Demonstrates changes in brain activity, therapeutic window and M1 receptor selectivity
LONDON, UK I February 10, 2016 I Heptares Therapeutics (“Heptares”), the wholly-owned subsidiary of Sosei Group Corporation (TSE Mothers Index: 4565), announces positive findings from its Phase 1b clinical study with HTL9936. HTL9936 is the first selective muscarinic M1 receptor agonist, designed using Heptares StaR® technology, which has entered clinical development as a new treatment for cognitive impairment in patients with dementia and schizophrenia.
These positive results provide strong evidence of a therapeutic window for the selective M1 agonist mechanism in general, and for progression of HTL9936 and similar molecules as medicines to treat cognitive disorders.
The Phase 1b precision medicine study involved 28 healthy elderly subjects who received different doses of HTL9936 and was designed to test the effect of drug on measures of brain activity while simultaneously monitoring side effects.
In the study, HTL9936 exhibited robust and statistically significant changes in brain electrical activity measured using multiple electroencephalography (EEG) biomarkers relevant to cognition, including effects on the P300 evoked response potential (p=0.0052). These pro-cognitive effects were seen at low doses and low blood concentrations that were safe and well tolerated.
M1 receptor selectivity was also confirmed across the dose range studied through the absence of gastrointestinal side-effects (such as diarrhoea and vomiting) typically attributed to the stimulation of M2 and M3 receptors. Such side effects are dose-limiting in standard-of-care acetylcholinesterase inhibitors, which likely work through non-selective muscarinic receptor stimulation.
Heptares is also developing a second patentably distinct M1 agonist, HTL18318, which is in Phase 1 and for which results are expected later this year. Phase 2 studies in dementia and schizophrenia patients are expected to commence in late 2016.
“The results from this Phase 1b study reinforce our earlier findings from clinical and preclinical studies, providing compelling evidence to support the therapeutic potential of Heptares’ selective M1 agonists for improving cognitive function in patients with dementia and schizophrenia,” commented Tim Tasker, Chief Medical Officer of Heptares. “We are excited by these findings and look forward to progressing the M1 programme into patient studies later this year.”
Malcolm Weir, Heptares CEO, added: “We are greatly encouraged by these findings from our lead M1 agonist programme. We have generated a diverse portfolio of selective agonists that includes not only M1 but M4 agonists for treating psychosis in schizophrenia and Alzheimer’s disease patients, and dual M1/M4 agonists for both psychosis and cognitive impairment in these patients; we expect these to reach the clinic from early 2017 onwards. We believe this is a programme with the potential to deliver medicines of immense clinical and commercial significance.”
About M1 Receptor Agonism
Direct M1 receptor agonism is a highly validated mechanism of action for improving cognitive function (memory and thinking) in patients with progressive dementia. By stimulating directly the pro-cognitive M1 receptors on nerve cells in the brain, M1 agonists substitute for the diminishing levels of the neurotransmitter (acetylcholine) in patients that normally act on these receptors. Previous attempts lacked selectivity and were discontinued due to M2 and M3 mediated side effects.
By contrast, HTL9936 and HTL18318 are small molecules designed using the Company’s proprietary structure-based platform (StaR® technology) and are highly selective for M1 over M2 and M3, therefore offering the prospect of a therapeutic window between enhanced cognitive activity and side-effects.
About Cognitive Impairment in Alzheimer‘s Disease and other CNS Diseases*
Today there is significant unmet medical need and heavy economic burden across multiple diseases characterized by cognitive impairment and dementia. In Alzheimer’s disease (AD), currently available drugs provide limited and transient effects on cognition. Healthcare costs associated with AD and dementia (estimated at over $640 billion for North America, Western Europe and Asia-Pacific) including nursing home care, continue to grow dramatically and new therapies with better and more durable efficacy are urgently needed. It is estimated that over 45 million people worldwide have dementia (4.8 million in North America, 7.5 million in Western Europe, 3.6 million in Asia-Pacific) and this is expected to increase to over 130 million in 2050. Alzheimer’s disease is the most common cause of dementia and may contribute to 60-70% of cases. In addition, an estimated 85% of the 3.2 million schizophrenia patients in the US suffer from cognitive impairment, as well as 1.4 million patients in the US suffering from Lewy body dementia. Currently there are no approved therapies for treating cognitive impairment in schizophrenia.
About Psychosis in Schizophrenia and other CNS Diseases*
Schizophrenia is a severe psychiatric illness leading to disturbances of thought. ‘Positive symptoms’ include hallucinations and delusions are linked to changes in dopamine levels and are treated with current antipsychotics. However, these are poorly tolerated due to side effects such as weight gain. There are estimated to be over 21 million people with schizophrenia worldwide. In addition, 30-50% of AD patients can suffer from severe behavioural symptoms including psychosis, agitation and hallucinations as the disease progresses. Therapies including cholinesterase inhibitors are most commonly used but these have only moderate and transient benefit and the dose is limited by side effects. There is currently no cure.
*Sources: World Health Organization, Alzheimer‘s Disease International, National Institute of Mental Health, Lewy Body Dementia Association.
About Heptares Therapeutics
Heptares is a clinical-stage company creating transformative medicines targeting G protein-coupled receptors (GPCRs), a superfamily of 375 receptors linked to a wide range of human diseases. Heptares’ proprietary StaR® technology and structure-based drug design (SBDD) capabilities enable us to engineer and develop drugs for highly validated, yet historically undruggable or challenging, GPCRs. Using this approach, we are building an exciting pipeline of new medicines (small molecules and biologics) with the potential to transform the treatment of Alzheimer’s disease, schizophrenia, migraine, addiction, metabolic disease and other indications.
We have advanced our lead assets – the first-in-class selective muscarinic M1 receptor agonists – from the earliest stages of discovery into clinical development for treating cognitive impairment/dementia in Alzheimer’s disease and schizophrenia. Preliminary clinical results confirm the exquisite selectivity of these compounds for the M1 receptor over other subtypes in human subjects, reinforcing preclinical findings. Other proprietary and partnered candidates across multiple indications are progressing towards the clinic.
We have also entered partnerships for our novel candidates and technologies with leading pharmaceutical and biotechnology companies, including Pfizer, AstraZeneca, MedImmune, MorphoSys and Teva.
Heptares is a wholly owned subsidiary of Sosei Group Corporation. For more information, please visit http://www.heptares.com and http://www.sosei.com.
HEPTARES is a registered trademark in the EU, Switzerland, US and Japan;
StaR® is a registered trademark in the EU and Japan.
About Sosei
Sosei is a biopharmaceutical company originating from Japan but with global presence. Sosei’s primary business model is based on identifying novel and/or differentiated product assets or technology platforms and, through supporting these in preclinical and clinical development and establishing commercial partnerships, advancing new medicines to patients worldwide. For more information about Sosei, please visit http://www.sosei.com
SOURCE: Heptares Therapeutics
Post Views: 94
Demonstrates changes in brain activity, therapeutic window and M1 receptor selectivity
LONDON, UK I February 10, 2016 I Heptares Therapeutics (“Heptares”), the wholly-owned subsidiary of Sosei Group Corporation (TSE Mothers Index: 4565), announces positive findings from its Phase 1b clinical study with HTL9936. HTL9936 is the first selective muscarinic M1 receptor agonist, designed using Heptares StaR® technology, which has entered clinical development as a new treatment for cognitive impairment in patients with dementia and schizophrenia.
These positive results provide strong evidence of a therapeutic window for the selective M1 agonist mechanism in general, and for progression of HTL9936 and similar molecules as medicines to treat cognitive disorders.
The Phase 1b precision medicine study involved 28 healthy elderly subjects who received different doses of HTL9936 and was designed to test the effect of drug on measures of brain activity while simultaneously monitoring side effects.
In the study, HTL9936 exhibited robust and statistically significant changes in brain electrical activity measured using multiple electroencephalography (EEG) biomarkers relevant to cognition, including effects on the P300 evoked response potential (p=0.0052). These pro-cognitive effects were seen at low doses and low blood concentrations that were safe and well tolerated.
M1 receptor selectivity was also confirmed across the dose range studied through the absence of gastrointestinal side-effects (such as diarrhoea and vomiting) typically attributed to the stimulation of M2 and M3 receptors. Such side effects are dose-limiting in standard-of-care acetylcholinesterase inhibitors, which likely work through non-selective muscarinic receptor stimulation.
Heptares is also developing a second patentably distinct M1 agonist, HTL18318, which is in Phase 1 and for which results are expected later this year. Phase 2 studies in dementia and schizophrenia patients are expected to commence in late 2016.
“The results from this Phase 1b study reinforce our earlier findings from clinical and preclinical studies, providing compelling evidence to support the therapeutic potential of Heptares’ selective M1 agonists for improving cognitive function in patients with dementia and schizophrenia,” commented Tim Tasker, Chief Medical Officer of Heptares. “We are excited by these findings and look forward to progressing the M1 programme into patient studies later this year.”
Malcolm Weir, Heptares CEO, added: “We are greatly encouraged by these findings from our lead M1 agonist programme. We have generated a diverse portfolio of selective agonists that includes not only M1 but M4 agonists for treating psychosis in schizophrenia and Alzheimer’s disease patients, and dual M1/M4 agonists for both psychosis and cognitive impairment in these patients; we expect these to reach the clinic from early 2017 onwards. We believe this is a programme with the potential to deliver medicines of immense clinical and commercial significance.”
About M1 Receptor Agonism
Direct M1 receptor agonism is a highly validated mechanism of action for improving cognitive function (memory and thinking) in patients with progressive dementia. By stimulating directly the pro-cognitive M1 receptors on nerve cells in the brain, M1 agonists substitute for the diminishing levels of the neurotransmitter (acetylcholine) in patients that normally act on these receptors. Previous attempts lacked selectivity and were discontinued due to M2 and M3 mediated side effects.
By contrast, HTL9936 and HTL18318 are small molecules designed using the Company’s proprietary structure-based platform (StaR® technology) and are highly selective for M1 over M2 and M3, therefore offering the prospect of a therapeutic window between enhanced cognitive activity and side-effects.
About Cognitive Impairment in Alzheimer‘s Disease and other CNS Diseases*
Today there is significant unmet medical need and heavy economic burden across multiple diseases characterized by cognitive impairment and dementia. In Alzheimer’s disease (AD), currently available drugs provide limited and transient effects on cognition. Healthcare costs associated with AD and dementia (estimated at over $640 billion for North America, Western Europe and Asia-Pacific) including nursing home care, continue to grow dramatically and new therapies with better and more durable efficacy are urgently needed. It is estimated that over 45 million people worldwide have dementia (4.8 million in North America, 7.5 million in Western Europe, 3.6 million in Asia-Pacific) and this is expected to increase to over 130 million in 2050. Alzheimer’s disease is the most common cause of dementia and may contribute to 60-70% of cases. In addition, an estimated 85% of the 3.2 million schizophrenia patients in the US suffer from cognitive impairment, as well as 1.4 million patients in the US suffering from Lewy body dementia. Currently there are no approved therapies for treating cognitive impairment in schizophrenia.
About Psychosis in Schizophrenia and other CNS Diseases*
Schizophrenia is a severe psychiatric illness leading to disturbances of thought. ‘Positive symptoms’ include hallucinations and delusions are linked to changes in dopamine levels and are treated with current antipsychotics. However, these are poorly tolerated due to side effects such as weight gain. There are estimated to be over 21 million people with schizophrenia worldwide. In addition, 30-50% of AD patients can suffer from severe behavioural symptoms including psychosis, agitation and hallucinations as the disease progresses. Therapies including cholinesterase inhibitors are most commonly used but these have only moderate and transient benefit and the dose is limited by side effects. There is currently no cure.
*Sources: World Health Organization, Alzheimer‘s Disease International, National Institute of Mental Health, Lewy Body Dementia Association.
About Heptares Therapeutics
Heptares is a clinical-stage company creating transformative medicines targeting G protein-coupled receptors (GPCRs), a superfamily of 375 receptors linked to a wide range of human diseases. Heptares’ proprietary StaR® technology and structure-based drug design (SBDD) capabilities enable us to engineer and develop drugs for highly validated, yet historically undruggable or challenging, GPCRs. Using this approach, we are building an exciting pipeline of new medicines (small molecules and biologics) with the potential to transform the treatment of Alzheimer’s disease, schizophrenia, migraine, addiction, metabolic disease and other indications.
We have advanced our lead assets – the first-in-class selective muscarinic M1 receptor agonists – from the earliest stages of discovery into clinical development for treating cognitive impairment/dementia in Alzheimer’s disease and schizophrenia. Preliminary clinical results confirm the exquisite selectivity of these compounds for the M1 receptor over other subtypes in human subjects, reinforcing preclinical findings. Other proprietary and partnered candidates across multiple indications are progressing towards the clinic.
We have also entered partnerships for our novel candidates and technologies with leading pharmaceutical and biotechnology companies, including Pfizer, AstraZeneca, MedImmune, MorphoSys and Teva.
Heptares is a wholly owned subsidiary of Sosei Group Corporation. For more information, please visit http://www.heptares.com and http://www.sosei.com.
HEPTARES is a registered trademark in the EU, Switzerland, US and Japan;
StaR® is a registered trademark in the EU and Japan.
About Sosei
Sosei is a biopharmaceutical company originating from Japan but with global presence. Sosei’s primary business model is based on identifying novel and/or differentiated product assets or technology platforms and, through supporting these in preclinical and clinical development and establishing commercial partnerships, advancing new medicines to patients worldwide. For more information about Sosei, please visit http://www.sosei.com
SOURCE: Heptares Therapeutics
Post Views: 94
